Distribution of LGR5+ cells and associated implications during the early stage of gastric tumorigenesis

PloS One
Bo Gun JangWoo Ho Kim

Abstract

Lgr5 was identified as a promising gastrointestinal tract stem cell marker in mice. Lineage tracing indicates that Lgr5(+) cells may not only be the cells responsible for the origin of tumors; they may also be the so-called cancer stem cells. In the present study, we investigated the presence of Lgr5(+) cells and their biological significance in normal human gastric mucosa and gastric tumors. RNAscope, a newly developed RNA in situ hybridization technique, specifically labeled Lgr5(+) cells at the basal glands of the gastric antrum. Notably, the number of Lgr5(+) cells was remarkably increased in intestinal metaplasia. In total, 76% of gastric adenomas and 43% of early gastric carcinomas were positive for LGR5. Lgr5(+) cells were found more frequently in low-grade tumors with active Wnt signaling and an intestinal gland type, suggesting that LGR5 is likely involved in the very early stages of Wnt-driven tumorigenesis in the stomach. Interestingly, similar to stem cells in normal tissues, Lgr5(+) cells were often restricted to the base of the tumor glands, and such Lgr5(+) restriction was associated with high levels of intestinal stem cell markers such as EPHB2, OLFM4, and ASCL2. Thus, our findings show that Lgr5(+) cells are pr...Continue Reading

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Citations

Aug 20, 2015·International Journal of Molecular Sciences·Werner Hoffmann
Jul 28, 2015·Histopathology·Bo Gun JangGyeong Hoon Kang
Mar 5, 2016·Cancer Investigation·Zhihao ZhangXiaoyan Zhao
Aug 6, 2015·Virchows Archiv : an International Journal of Pathology·Bo Gun JangWoo Ho Kim
Sep 22, 2015·Clinics and Research in Hepatology and Gastroenterology·Tianchen HuangDongxiao Bai
Sep 21, 2015·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Bo Gun JangWoo Ho Kim
Apr 18, 2015·Journal of Hematology & Oncology·Axel SchulenburgPeter Valent
Apr 27, 2016·Nature Reviews. Cancer·Yoku HayakawaTimothy C Wang
Jan 4, 2017·Human Pathology·Bo Gun JangGyeong Hoon Kang
Sep 28, 2017·Cancer Biomarkers : Section a of Disease Markers·Elham KalantariZahra Madjd
Jan 11, 2017·Virchows Archiv : an International Journal of Pathology·Bo Gun JangWoo Ho Kim
Sep 7, 2016·Pathology International·Tomoyuki NakajimaHiroyoshi Ota
Mar 19, 2016·Colorectal Disease : the Official Journal of the Association of Coloproctology of Great Britain and Ireland·A Morley-BunkerT Eglinton
Feb 22, 2017·Molecular Cancer Research : MCR·Franziska WilhelmChristoph Röcken
Jan 20, 2021·Clinical and Translational Gastroenterology·Azfar NeyazVikram Deshpande
Apr 12, 2020·Pathology, Research and Practice·Sun-Young JunSeung-Mo Hong
May 1, 2021·Genes·Felicitas MungenastRupert C Ecker

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Methods Mentioned

BETA
dissection
biopsies
PCR
laser capture microdissection

Software Mentioned

GraphPad
Prism
RNAscope
7500 system SDS
PASW
SPSS

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